Naslov
ANTISTEATOTIC EFFECT OF LIRAGLUTIDE IS MEDIATED THROUGH ACSL1 and SREBP-1c SIGNALING PATHWAY IN A CELL CULTURE MODEL OF TAMOXIFEN-INDUCED STEATOSIS

Autori
Omanović Kolarić, Tea ; Ninčević, Vjera ; Kizivat, Tomislav ; Kuna, Lucija ; Zjalić, Milorad ; Bilić- Ćurčić, Ines ; Smolić, Robert ; Roguljić, Hrvoje ; Petrović, Ana ; Včev, Aleksandar ; Wu, George ; Smolić, Martina

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Pharmaca Glasilo Hrvatskog društva za kliničku farmakologiju i terapiju Hrvatski časopis za farmakoterapiju / - , 2022, 172-172

Skup
10. hrvatski kongres farmakologije ; 1. hrvatski kongres kliničke farmakologije s međunarodnim sudjelovanjem = 10th Croatian Congress of Pharmacology ; 1st Croatian Congress of Clinical Pharmacology and Therapeutics with International Participation

Mjesto i datum
Opatija, Hrvatska, 22.09.2022. - 25.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Recenziran

Ključne riječi
liraglutide ; tamoxifen ; non-alcoholic fatty liver disease ; Huh7 cell culture

Sažetak
Introduction: Nonalcoholic fatty liver disease (NAFLD) has become one of the global health problems. Drugs, such as tamoxifen, may trigger or exacerbate pre-existing NAFLD. The aim of our study was to establish a reliable cell culture model of tamoxifen-induced steatosis (TIS) and to investigate a possible antisteatotic effect of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide in this model. Materials and methods: The cell culture model of drug-induced hepatic steatosis was established by incubating Huh7 cells, a human liver cell line expressing the GLP- 1 receptor, with 2 μM tamoxifen for 24 hours. Cells were co-treated with 5 nM to 20 nM liraglutide. Cell survival was measured by the erythrosin B staining exclusion assay, and changes in cell shape and the extent of hepatosteatosis were assessed by fluorescence microscopy with Oil- Red-O (ORO) and DAPI staining, respectively. The expression of various lipogenic genes and signals was assessed by RT-PCR. Results: Tamoxifen significantly decreased cell survival in the TIS model (p < 0, 05), and concurrent treatment with liraglutide had no significant effect. A 5-fold increase in lipid accumulation was observed by ORO staining in the TIS model (p < 0, 001), which was due to the significant increase in the number of lipid droplets. However, liraglutide reversed this effect and significantly decreased the number of lipid droplets (p < 0, 05). Liraglutide co- treatment significantly ameliorated the lipogenic ACSL1 and SREBP-1c gene expression signaling pathways, which were increased in the TIS model (p < 0, 001). Conclusions: Liraglutide ameliorates microsteatotic changes observed in TIS model by downregulation of ACSL1 and SREBP-1c gene pathways.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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